title: The howling cortex: seizures and general anesthetic drugs.
abstract: The true incidence of seizures caused by general anesthetic drugs is unknown. Abnormal movements are common during induction of anesthesia, but they may not be indicative of true seizures. Conversely, epileptiform electrocortical activity is commonly induced by enflurane, etomidate, sevoflurane and, to a lesser extent, propofol, but it rarely progresses to generalized tonic-clonic seizures. Even "nonconvulsant" anesthetic drugs occasionally cause seizures in subjects with preexisting epilepsy. These seizures most commonly occur during induction or emergence from anesthesia, when the anesthetic drug concentration is relatively low. There is no unifying neural mechanism of anesthetic drug-related seizurogenesis. However, there is a growing body of experimental work suggesting that seizures are not caused simply by "too much excitation," but rather by excitation applied to a mass of neurons which are primed to react to the excitation by going into an oscillatory seizure state. Increased gamma-amino-butyric acid (GABA)ergic inhibition can sensitize the cortex so that only a small amount of excitation is required to cause seizures. This has been postulated to occur 1) at the network level by increasing the propensity for reverberation (e.g., by prolongation of the "inhibitory lag"), or 2) via different effects on subpopulations of interneurons ("inhibiting-the-inhibitors") or 3) at the synaptic level by changing the chloride reversal potential ("excitatory GABA"). On the basis of applied neuropharmacology, prevention of anesthetic-drug related seizures would include 1) avoiding sevoflurane and etomidate, 2) considering prophylaxis with adjunctive benzodiazepines (alpha-subunit GABA(A) agonists), or drugs that impair calcium entry into neurons, and 3) using electroencephalogram monitoring to detect early signs of cortical instability and epileptiform activity. Seizures may falsely elevate electroencephalogram indices of depth of anesthesia.
authors.affiliation: Department of Anesthesia, Waikato Clinical School, Waikato Hospital, Pembroke St, Hamilton, New Zealand.
authors.forename: Logan J
authors.initials: LJ
authors.lastname: Voss
authors.forename: James W
authors.initials: JW
authors.lastname: Sleigh
authors.forename: John P M
authors.initials: JP
authors.lastname: Barnard
authors.forename: Heidi E
authors.initials: HE
authors.lastname: Kirsch
mesh_terms: D000758:Anesthesia / Q000009:adverse effects; D018681:Anesthetics, General / Q000009:adverse effects*; D000818:Animals; D004421:Dystonia / Q000139:chemically induced; D004569:Electroencephalography / Q000187:drug effects; D004827:Epilepsy / Q000139:chemically induced*; D006801:Humans; D007649:Ketamine / Q000009:adverse effects; D009043:Motor Activity / Q000187:drug effects; D015742:Propofol / Q000009:adverse effects; D012640:Seizures / Q000139:chemically induced*
chemical_list: D018681:Anesthetics, General; D007649:Ketamine; D015742:Propofol